Calcitonin driven v-Ha-ras induces multilineage pulmonary epithelial hyperplasias and neoplasms.
Calcitonin driven v-Ha-ras induces multilineage pulmonary epithelial hyperplasias and neoplasms.
复制标题
降钙素驱动的 v-Ha-ras 诱导多谱系肺上皮增生和肿瘤。
作者：
Sunday,ME;Haley,KJ;Sikorski,K;Graham,SA;Emanuel,RL;Zhang,F;Mu,Q;Shahsafaei,A;Hatzis,D
我们使用由神经/神经内分泌（NE）特异性降钙素启动子（rascal）驱动的v-Ha-ras建立了原发性肺神经内分泌细胞（PNEC）增生/肿瘤的转基因模型。此前，我们发现亚硝胺治疗的啮齿动物会出现 PNEC 增生，但会出现非 NE 肺部肿瘤，其不同的结果可能反映了多个细胞谱系中 ras 的激活。有趣的是，所有 rascal 转基因小鼠谱系均出现 NE 和非 NE 细胞增生，但大多数为非 NE 肺癌，在分化的 PNEC 和肿瘤细胞中具有 rascal mRNA。对胚胎肺的分析表明，未分化上皮中存在 rascal mRNA，与常见的多能前体细胞中的表达一致。这些意想不到的观察结果表明，v-Ha-ras 可导致体内 NE 和非 NE 增生/肿瘤，为肺癌发生的研究开辟了新途径。
We initiated a transgenic model for primary pulmonary neuroendocrine cell (PNEC) hyperplasia/neoplasia using v-Ha-ras driven by the neural/neuroendocrine (NE)-specific calcitonin promoter (rascal). Previously, we showed that nitrosamine treated rodents develop PNEC hyperplasia but non-NE lung tumors, with variable outcomes presumably reflecting ras activation in multiple cell lineages. Interestingly, all rascal transgenic mouse lineages develop hyperplasias of NE and non-NE cells but mostly non-NE lung carcinomas, with rascal mRNA in differentiated PNECs and tumor cells. Analyses of embryonic lung demonstrate rascal mRNA in undifferentiated epithelium, consistent with expression in a common pluripotent precursor cell. These unexpected observations indicate that v-Ha-ras can lead to both NE and non-NE hyperplasia/neoplasia in vivo, opening new avenues for studies of lung carcinogenesis.